The Efficiency of Bacterial Vaccines on Mortality during the ‘Spanish’ Influenza Pandemic of 1918–19

Summary The worldwide ‘Spanish’ influenza pandemic of 1918–19, which extended into the 1920s, infected more than a third of the world’s population and killed an estimated 50–100 million people, more than the civilian and military casualties of World War I. Present-day medical scholars, journalists, and other commentators have often ignored, downplayed or treated with scepticism the role of bacterial vaccines in reducing mortality during the pandemic. There have been repeated claims in this century that these vaccines were ‘useless’, ‘concocted’, and possibly harmful. Focussing on the Australian scene, I show that bacterial vaccines from reputable sources did indeed reduce mortality, perhaps to a greater extent in some cases than modern anti-viral influenza vaccines.

commentary gives a misleading picture of the state of medical knowledge at the period, the understanding of the immediate causes of death, the methodology of vaccine trials and the effectiveness of these pharmaceutical interventions.To refute these claims, I first discuss what we know of the state of knowledge about viruses, vaccines and causes of death in 1918-19.A number of evidently successful vaccine trials during the pandemic are then examined.The results suggest that the effectiveness of these vaccines against mortality was comparable with that of some modern day influenza vaccines.It follows that the health authorities and medical experts of the day were not as uninformed or naïve as some modern critics suggest.

Criticisms of the 1918-19 Bacterial Vaccines
There are several common threads in contemporary criticisms of the pandemic vaccines and studies of their effectiveness.Firstly, as seen in the above History of Vaccines post, 3 it is argued that bacterial vaccines could have had no effect because the medical workers of the time did not realise that the causative agent of influenza was a virus, and not a bacterium.
Miles Ott and his colleagues state that the two bacterial vaccines used in Minnesota were not effective as they did not contain the influenza virus. 4The 'tremendous enthusiasm' for using vaccines exceeded by far the scientific knowledge and technological capacity of the day, according to Jason Schwartz. 5In a 2014 Lancet Respiratory Medicine article, Hannah Cagney claims that the vaccines were 'completely ineffective' because they were based on 'bacteriological theories'. 6Martin Gorsky and his associates argue that because contemporary medical authorities did not realise that influenza was a virus, the efficacy of the vaccines was limited, 'except possibly against secondary infections'. 7ome studies ignore, downplay or deny the use of bacterial vaccines.The possible effects of mass vaccination on mortality are not mentioned in a study by Peter Caley and his co-authors on the role of social distancing in saving lives during the pandemic in Sydney, Australia.Perhaps half of the population of New South Wales (NSW) had been inoculated with a state-provided bacterial vaccine against influenza by May 1919. 8ori Loeb, in  not discuss vaccines although many military persons were inoculated. 9There were no vaccines to help the pandemic's victims in California, according to Diane North. 10 Sandra Tomkins claims incorrectly that there were 'no vaccines or specific cures for influenza' in 1918-19.She writes that effective vaccines had to await the discovery of its virus in 1933. 11Implicit in her claim is the assumption that the immediate causes of death were not bacterial.
Another thread of criticism is the claim that bacterial vaccines were probably ineffective because they could not have contained a sufficient spectrum of the strains or serotypes of virulent bacteria currently prevalent in persons diagnosed with influenza.The use of current variants of bacteria is important because immunity to a given strain or serotype of the same species may not mean immunity to another strain or serotype. 12As Dennis Shanks writes: 'It is also difficult to see how such a mixed [bacterial] vaccine could generate an antibacterial immune response'. 13John Oxford and Douglas Gill maintain that no-one knew at the time that there were multiple serotypes of Pneumococci. 14We now know, for example, that Streptococcus pneumoniae, one of the components of the mixed-bacteria vaccines, has more than 90 serotypes. 15American virologist Stanley Plotkin expressed a similar view in the Philadelphia College of Physicians blog in 2018. 16 related approach is the use of loaded and emotive terms for the vaccines, their development, and their manufacture.Vaccines were said to have been 'crude', or in some cases 'witches' brews of injectable fluids'. 17 third line of criticism is that the studies of vaccine outcomes at the period were fundamentally unsound because they did not follow present-day standards for evaluation of medical trials. 18This means that reports of successes during 1918 and 1919 meet with deprecating or sceptical commentary.The methodological weaknesses of the 1918-19 studies include selection bias, unequal exposure to risk and unsatisfactory reporting of outcomes. 19Other deficiencies were the timing of vaccinations with respect to waves of infection and failure to account for confounding factors such as differing treatment regimes. 20John Eyler claims that better controlled studies, where risks of infection were more equalised between inoculated and uninoculated subjects, were less likely to conclude that the vaccine was effective.But I agree nevertheless with Eyler's view that '[s]uch retrospective methodological criticism is unfair and ahistorical'.The criticism is unfair because careful testing was impossible because physicians were inexperienced in the conduct of trials and health resources were 'stretched to the limit'.It is ahistorical because physicians were judged according to standards which did not then exist. 21

The State of Vaccine Technology in 1918-19
Vaccination was a well-established technology by 1918.Indeed it had been practised for hundreds of years, the best known example being Edward Jenner's successful inoculations in the 18th century against the smallpox virus using preparations of the much milder cowpox. 22Jenner's program was pragmatic and not based on theory.Its widespread adoption and its endorsement by the British parliament indicate that his vaccine was reasonably effective. 23Although the germ theory of disease had been established since the mid-nineteenth century, Robert Koch, a German physician, became the first to link a specific bacterium to a specific disease in 1876.Koch's use of solid culture media for growing bacteria and microscopy were ground-breaking developments. 24Although Koch's reputation as a medical scientist was adversely affected by his unsuccessful tuberculosis vaccine, this vaccine was nevertheless developed into a useful diagnostic aid in the 20th century. 25Serums derived from the blood of animals immune to the targeted disease could also confer immunity.Emil von Behring and Shihasaburo Kitasato, working at Koch's Institute for Hygiene in Berlin, developed the first serums for diphtheria and tetanus. 26t around the time of Koch's ground-breaking work, Louis Pasteur, an eminent French scientist, was experimenting with transmission of bacterial infections among poultry via inoculation.He and his co-researchers found that killed or weakened (attenuated) bacteria did not kill the host and conferred immunity. 27Pasteur's vaccines for anthrax in livestock and fowl cholera were highly successful. 28The human cholera vaccine, developed by Waldemar Haffkine at Pasteur's Institute in Paris, proved to be effective in the Indian epidemics of the 1890s. 29Pasteur also applied the attenuation technique for the preparation of an effective vaccine against viral rabies.Stock serums against Pneumococcus bacteria appeared in the H. K. Mulford catalogue in 1895. 30The British bacteriologist Almroth Wright ran the first trial of a whole-cell heat-killed Pneumococcus vaccine from 1911 to 1912.While earlier trials among South African miners did not produce significant results, a trial in late 1912 with a higher concentration of bacteria reduced the death rate by 40 to 50 per cent.Pneumococcal vaccines using a mixture of serotypes were deployed early in the pandemic with 'Spanish' influenza patients at United States Army Camps Wheeler and Upton.They apparently reduced mortality markedly. 31accination was by no means a new and untried technology in 1918.And anti-bacterial vaccines still play a role up to the present day in reducing secondary infections. 32So it is puzzling that there has been so little recognition that the bacterial vaccines of 1918-19 might have played a similar role.
As noted earlier, critics have stressed the methodological weaknesses (by modern standards) of some influenza vaccine trials.It does not follow that researchers from the late 19th century were necessarily uninformed about the latest statistical methods and the value of avoiding selection bias.The Pasteur Institute employed statistical techniques extensively in their studies of tetanus, typhoid, gangrene, typhus and staphylococci in the decades preceding World War I.In 1898, Johannes Fibiger, a Danish physician, conducted a genuine randomised trial of an anti-diphtheria serum. 33But Ronald Fisher, an eminent British statistician, did not publish the theoretical statistical advantages in experimental design of random allocation until 1925 in his definitive work Statistical Methods for Research Workers. 34Researchers from the 19th century had long advocated 'alternate allocation' to treatment comparison groups as a means to avoid selection bias. 35

The Understanding of Viruses as of 1918-19
In 1881 Pasteur wrote that 'the virus is a microbial parasite, which may be multiplied by cultivation outside the body of an animal'. 36The first understandings of viruses, as now we know them, were obtained via a filter developed by in Pasteur's laboratory by Charles Chamberland in 1884, which was used to remove bacteria from liquids.By the 1900s the Chamberland-Pasteur filter was in widespread use to deliver potable water. 37This device allowed the Russian botanist Dmitri Iwanowski to determine in 1892 that the disease-causing agent for tobacco mosaic disease was not bacterial. 38Martinus Beijerinck, a Dutch botanist, proposed that these filter-passing 'microbes', which were invisible to the microscopes of the day, should be called viruses.By 1906, 18 filter-passing agents associated with plant, animal and human diseases had been identified. 39The term 'virus' (in Pasteur's sense) had been widely used in medical articles in the press well before the influenza pandemic. 40n October 1918 John Bradford, Ernest Bashford and J. A. Wilson, medical researchers for the British Army, claimed that they were able to culture a filter-passing virus derived from the blood of patients with acute and severe influenza.This finding was reported in the British Medical Journal (BMJ) on 1 February, 1919 and was widely reported in the Australian press as the discovery of 'the influenza virus' within a week. 41This speed of dissemination suggests that Australia was well in touch with recent scientific developments.The term 'influenza virus' was frequently used in Australian newspaper articles after the BMJ report. 42But Bradford et al.'s claims of an isolatable disease agent were rebutted on methodological grounds by the end of the year.J. A. Arkwright examined their filtered preparations of sputum from influenza patients and found that they were contaminated with disease-causing bacteria, and that control samples appeared identical to the filtered samples.Although animals inoculated by Bradford's team with the filtered samples did show signs of disease, Arkwright contended that the contamination made it impossible to prove that their sickness was caused by influenza.In the same issue of the BMJ, both Bradford and Wilson accepted that their claims were not proven. 43rkwright suggests that the experimental failings of Bradford and his colleagues were likely due to rushed work under wartime conditions. 44Evidence for an isolatable influenza virus in humans was not generally accepted until the work of Wilson Smith and his colleagues in 1933. 45Yet it seems clear that researchers in 1919 understood that viruses were disease causing agents which could not be observed in the microscopes of the time.W. G. Armstrong, an Australian researcher, postulated that the agent was a 'minute organism'.J. Rose Bradford, a British researcher, had claimed that the actual agent was a bacillus. 46Researchers had indeed isolated filter-passing agents for other conditions, as noted above, despite the problematic work of Bradford et al in the case of influenza.

The Causes of Death
During the 'Russian' influenza of the 1890s, Richard Pfeiffer, a German bacteriologist, claimed that Bacillus influenzae, which he had found in infected patients, was the actual cause of disease and death.This bacterium was later called Pfeiffer's bacillus or Haemophilus influenzae.But by late 1918 this association had been discredited.Although initial trials in 1918 with single H. influenzae vaccines had been reported as successful, other researchers had had difficulty in isolating the bacillus from influenza patients.The most common organisms found were Pneumococci or Streptococci. 47aking a precautionary approach, physicians lost confidence in H. influenzae vaccines and moved to mixed-bacteria preparations.Some omitted H. influenzae altogether. 48evertheless this bacterium is still seen as a cause of pneumonia.According to Eva Heinz, 21st century studies of the prevalence of the Hib type of this bacteria (then the majority type), showed that Hib vaccines had almost eradicated this form of pneumonia in some countries by the end of the 20th century. 49arly in the pandemic, physicians became aware that influenza itself was not necessarily the immediate cause of death.They did recognise that it was the primary or underlying cause of pandemic deaths; that is to say that these deaths would not otherwise have occurred without this initial infection.But published data from the period suggest that the immediate cause of the great majority of deaths was a secondary haemorrhagic bacterial infection of the lungs. 50Milton Winternitz and his associates, writing in 1920, suggested that the 'unknown etiological agent in influenza' injured the lungs, so that bacteria resident in the body could initiate infections such as pneumonia. 51Indeed, the official, medical and lay terminology for the disease at the time was 'pneumonic influenza'. 52Swabs from living and deceased patients revealed the presence of a range of species of bacteria thought to be associated with fatal cases of pneumonia, including strains of Pneumococci, Streptococci, Staphylococci and Diplococci. 53These microbes were known at the time to be present in the respiratory tracts of healthy persons. 54Physicians reasoned that influenza infection had weakened the body's defences, in particular, the lining of the lung.Hence these bacteria, in killed or weakened formulations, were seen as eligible candidates for effective vaccines, even though the medical profession suspected that these bacteria were not the underlying or primary causes of death and illness.

The 1918-19 Studies of Mixed Bacteria Vaccines
There were apparent successes with mixed vaccines.Edward Rosenow, a pulmonary specialist based in Rochester, Minnesota, formulated a mixture of killed pneumococci, haemolytic streptococci, staphylococci and Pfeiffer's bacillus.When he was convinced that the vaccine was safe and effective in small scale trials, it was distributed by the Mayo Foundation to physicians, hospitals and other institutions within a 320 kilometre radius.Three doses were given.Rosenow found that the mortality rate in Minnesota for the unvaccinated control patients was about four times greater than the rate for the fully vaccinated. 55But George McCoy, Director of the Hygienic Laboratory of the United States Public Health Service, and his associates concluded from a trial in a single state insane asylum that Rosenow's vaccine was a 'failure'.Eyler contrasts the superior methodology of McCoy's study with respect to equalisation of risk as compared to the general methods of other studies of the time. 56Yet a 2009 metastudy of pandemic vaccine studies by Yu-Wen Chien and her colleagues found that Rosenow's vaccine was protective, as I discuss later. 57 seemingly successful mixed vaccine, however, broadly similar in composition to Rosenow's and containing Pfeiffer's bacillus, was developed by the Australian government owned Commonwealth Serum Laboratories (CSL) in Melbourne in late 1918.58 CSL had been set up in 1916 to address wartime shortages of vaccines and other medical supplies.59 It is clear from the detailed description by its first director, W. J. Penfold, that the vaccine's preparation used the most advanced technology of the day, for example in the painstaking measures taken to avoid contamination of the culture media for the growth of bacteria derived from patient samples.60 It could not be described as a 'witches brew'.61 Thomas Cherry, a noted Australian bacteriologist, found that trials of the CSL vaccine in isolation hospitals in Melbourne from late January to the middle of March 1919 showed a 3:1 reduction in the overall death rate for inoculated versus uninoculated patients (4.0 per cent as against 13.8 per cent).62 Positive results were also claimed for the CSL vaccine when it was used in the Samoan relief expedition of December 1918, led by Surgeon Lieutenant Francis Grey.Responding to an urgent call for help in November, a medical team with vaccine supplies was sent from Australia in quick time.While en route, the vaccine was also issued to the crew of the relief ship, HMAS Encounter.But when the expedition arrived, about a quarter of the indigenous population had already died and, according to Shanks, the epidemic was waning. Gry noted that the case mortality rate for resident Europeans was only two per cent. Shnks claims that no actual figures were produced for the CSL vaccine's effectiveness in Samoa.I have already mentioned his scepticism about the usefulness of mixed bacterial vaccines.Yet by the time the Encounter's crew had returned to Sydney, at the height of the first wave of the pandemic in that city in March 1919, 22 per cent had been ill, but none of them contracted pneumonia or died.63 During the first half of 1919, Gray observed that of the 2,875 sailors inoculated at the Williamstown naval base in Melbourne, only 345 were infected and none died.64 Significant reductions in mortality were observed in New South Wales public hospitals with the CSL vaccine or with the similar 'state' vaccine, which incorporated some serums supplied by CSL.Among 13,000 patients treated for influenza, mortality among the unvaccinated was 16.5 per cent, while the mortality for the vaccinated was 10.7 per cent for all persons who had received at least one inoculation.65 A study of 1,401 patients in Melbourne public isolation hospitals admitted between the end of January 1919 and the middle of March showed that the overall mortality of unvaccinated persons was more than twice the mortality of the vaccinated (9.3 per cent versus 3.9 per cent).Patients hospitalised in the early days of infection had a much lower death rate, whether vaccinated or not.66 With respect to the above-mentioned critiques about the use of relevant bacterial variants in the vaccines, CSL made a determined effort to secure as many strains as possible from current or deceased patients.For example, 170 cultures of pneumococcus-like organisms from 97 different sources were used in the vaccines, while 27 cultures of streptococcus from 20 sources were also included.Swabs were taken mainly from Victorian patients, with some provided from the North Head quarantine station in Sydney.It should be noted that CSL found significant numbers of Pfeiffer's bacillus (H.influenzae) in the lungs and that this bacterium was included in the vaccine. 67For indigenous Australians living in remoter areas, we can assume that vaccines and other medical interventions came late or not at all.In Queensland, about 30 per cent of all reported influenza deaths were among Aboriginal people, approximately two per cent of the estimated Indigenous population in that state.Gordon Briscoe attributes the high death rate to lack of immunity among people in remote settlements. Inigenous people from these communities were forced to move to makeshift hospital 'camps' for treatment where they received little or no care, poor nutrition, were exposed to other infections and had minimal shelter.68 We can infer from this poor standard of care that Aboriginal communities, in Queensland at least, were likely not included in influenza vaccination campaigns.69 From the chaos which Briscoe describes when many deaths occurred on the same day, it is probable that the death rate was significantly undercounted.70 Indigenous peoples around the world suffered disproportionate death rates as compared to Europeans, especially among young adults.71 In some Indigenous communities in Alaska the mortality rate was greater than 80 per cent.Children were the only survivors in some Arctic villages.72 There were other evident successes for mixed vaccines in Canada and Britain.A vaccine was prepared by Fred Cadham in 1919 for the treatment of soldiers suffering from influenza at the Tuxedo Medical Hospital in Winnipeg, Canada.Cadham found that no military patient died who had received two doses, whereas 17 died among the 238 uninoculated patients.The average hospital stay was twice as long for the unvaccinated.About a quarter of the civilian populations in Manitoba and Saskatchewan who were inoculated received Cadham's vaccine, while the remainder were given the Rosenow vaccine.Among the approximately 53,000 vaccinated civilians in these provinces, the death rate for the twice inoculated was about half that for those vaccinated once only, and about a seventh of the mortality rate for notified, unvaccinated patients.Cadham did not mention any attempt to match the civilian control group with the vaccinated subjects.73 A mixed vaccine recommended by William Leishman, Director of Pathology at the War Office in London, was given to 15,624 military personnel, whereas 43,520 were not vaccinated.The death rate in the control group was about 12 times the death rate in the vaccinated group.Although the test was poorly controlled by modern standards, both groups were similar in age and health.74 As with the CSL vaccines, the bacteria used in these Canadian and British vaccines were all derived from influenza patients within the general area of the manufacturing laboratories.

For-Profit Vaccines
There was substantial 'boosting' of for-profit bacterial vaccines at this period in the USA and Australia.For example, there were many advertisements for proprietary vaccines and influenza 'cures' in Australian newspapers.Donald Ross and Company of Sydney, which also marketed veterinary vaccines, offered a 'Pneumococcic-Influenzal' vaccine. 75ustralian doctors were advised in February 1919 that ample supplies of vaccine were available from Elliott Brothers Surgical Department in Sydney. 76An 'unlimited quantity' was available from Francois Ray's Vaccine Institute in Sydney.Ray, a French bacteriologist, was probably a reputable source, having worked with Pasteur in Paris.Arriving in Sydney in 1911 as the Pasteur Institute's representative in Australia, he founded his own institute sometime before 1918. 77The Biological Institute of Australasia, a private company, offered a 'high concentration of specific pneumococci organisms' in its vaccine, costing £1 per tube of double inoculations, not including the doctor's profit margin.78Some anti-vaccination voices at the period accused private suppliers of reaping a 'bonanza' from a credulous public. 79Presumably these more expensive offerings, which would likely have attracted the anxious and wealthy, might have been seriously undercut by the free CSL vaccine offered in the mass vaccination drives of local councils in Victoria and New South Wales which were co-ordinated by the public health authorities.These campaigns were substantially assisted by thousands of unpaid volunteers. 80n the USA, private drug companies promoted vaccines which had been in stock for some years, including preventatives against the common cold.If these older vaccines did perchance contain killed bacteria associated with the secondary infections of the pandemic, they were unlikely to be effective because they probably were not up-to-date with the strains and serotypes present in 1918 due to evolutionary processes over time.We know now that pathogens, including pneumonia bacteria, can rapidly alter their strain dynamics and serotype composition in response to genotype changes in their hosts as the latter develop resistance. 81ccording to Eyler, there was also a great deal of 'price-gouging' by commercial interests and 'hucksterism' by individual medical practitioners.Max Exner, author of several books on sexuality, issued 'glowing testimonials' to his own successful use of an omnibus vaccine for influenza, blood poisoning and pneumonia.This vaccine had been developed six years earlier by Ellis Bonime at the Polyclinic Medical School in New York.Its contents were undisclosed. 82G. H. Sherman of Detroit marketed a mixed vaccine which claimed to 'abort' colds, influenza and pneumonia. 83The privately-owned Cutter Laboratories of Chicago declared that their mixed vaccine gave 'complete protection'. 84hile it is possible, as may have been the case with Ray's vaccine in Sydney, that some of these commercial vaccines were effective, their providers had an interest in advertising their own successes.There is minimal independent evidence available of the effectiveness of their offerings. 85

Vaccine Effectiveness and Efficacy: What They Mean and How They Are
Measured?
In order to make a comparison of the effectiveness of the 1918-19 vaccines in reducing mortality with the effectiveness of modern anti-viral influenza vaccines, a standard of measurement is required.Here I need to explain the technical terms vaccine efficacy and vaccine efficiency.According to the World Health Organization (the WHO), vaccine efficacy is a measure of the outcome of a controlled clinical trial where the unvaccinated group receives a placebo.Ideally, the 'gold standard' is a double-blind study, where neither the participants nor the inoculators know if the inoculation is the actual vaccine, and the selection of subjects is randomised.Vaccine efficiency, on the other hand, is a measure of the outcome in the 'real world', where the researchers have no control over who is selected for vaccination. 86Because the 1918-19 vaccine trials were poorly controlled or not controlled by modern standards, it seems that 'efficiency' is the more appropriate term to use for these studies.Nevertheless Chien and her colleagues preferred to use the term 'efficacy' in their 2009 metastudy.They conceded that none of the thirteen military and civilian studies they selected were double-blind randomised studies.But they evidently believed that the statistical techniques they used could compensate for the methodological deficiencies in the selected studies, allowing them to speak of 'efficacy'.Over 460 studies were not selected due to low sample sizes or insufficient information.Adjusting for publication bias (i.e., taking unpublished results into account), and confounding factors, Chien and her co-authors estimated that the efficacy for the remaining thirteen studies was about 34 per cent in preventing pneumonia and 42 per cent for case fatality. 87These data might be roughly compared with the estimated 30 per cent vaccine efficacy against mortality during the 1989-90 influenza epidemic in England. 88able 1 shows my estimates for the efficiency of selected 1918-19 vaccines, together with published estimates for these vaccines by Chien et al.I also show estimates for a modern influenza vaccine and COVID.For my calculations, I used standard formulae endorsed by the WHO for measuring either efficiency or efficacy of vaccines.These formulae, which have been in use since 1915, 89 are used to estimate the value of vaccines with respect to either death or infection rates. 90here ARU = the attack rate in the unvaccinated population and ARV = the attack rate in the vaccinated population.The attack rate for mortality is the percentage of an at-risk population that dies from the disease.
-OR -VE (%) = (1 -RR) × 100 where RR = relative risk, the probability of an event occurring in the treated group divided by the probability of the event in the untreated group.
The measures of efficiency and efficacy with respect to mortality in Table 1 suggest that the 1918-19 bacterial vaccines were roughly comparable with modern influenza vaccines.

Conclusions
Claims that physicians and researchers in 1918-19 had little or no knowledge either of the nature of viruses or of the immediate causes of death during the pandemic are not supported by the evidence.It is clear that many researchers had an understanding of viruses as causative factors for disease and death by 1918.They also understood that the immediate causes of the great majority of influenza deaths were bacterial secondary infections.While researchers could not establish a specific bacterium to be the cause of  97 death, vaccine makers took a conservative approach, using a range of species and strains found in significant numbers in patients.Oxford and Gill's claim that no one knew at the time that Pneumococcus had many serotypes is correct, but seems unfair in this context and beside the point in judging the effectiveness of vaccination.Physicians certainly knew that Pneumococcus and other bacteria had several strains and indeed used a range of types derived from current patients in vaccines.It is also clear that vaccine technology was well established and reasonably successful by 1918.Penfold's detailed account of the preparation of the CSL vaccine, for example, with its frequent references to international practices and research, undermines claims that the preparation of this vaccine was based on ignorance and incompetence rather than the latest science. 99espite the methodological weaknesses of the 1918-19 studies as seen from present-day perspectives, the evidence suggests that the mixed bacterial vaccines provided by reputable sources during the pandemic were reasonably effective in preventing mortality.Substantial differences in mortality between inoculated and uninoculated in a variety of jurisdictions cannot simply be dismissed en bloc as failures to conform to modern standards of medical trials.The health authorities and medical experts of the day were not uninformed, naïve or hapless with respect to pharmaceutical interventions for influenza, or the causes of mortality.As Michael Bresalier notes: 'Retrospective judgments of the failure of laboratory medicine to control influenza not only ignore the state of contemporary scientific knowledge and practices, but also how experts responded to the challenges'. 100espite a wave of historiography about the pandemic in this century which has critically re-examined or revealed a mass of evidence, 101 unfair sceptical commentary about the influenza vaccines, and the alleged misunderstandings of medical experts of the time, persist. 102It is curious that such critiques have not been focussed on other pre-1919 vaccines (viral and bacterial), such as the pneumonia vaccines discussed earlier. 103For these vaccines, their theoretical underpinnings, their trials and their standards of preparation, also did not meet modern standards.This forgetting may perhaps be explained when it is understood that most of today's effective vaccines began development during the 'Golden Age' of the 1950s.The most famous example was the Salk and Sabin vaccines for polio, available in the early 1960s. 104It is likely that the sheer bulk of more recent scientific knowledge, and the successes of later vaccines, have induced commentators to view the pandemic vaccines, and their developers, through a modern lens, rather than on their own terms.
her study of responses to influenza in Britain from 1889 to 1919, does

Table 1 .
Vaccine efficiencies and efficacies with respect to mortality